5.7 Abstract - CHEMICAL LIBRARY SCREENING (Core Group B) The Chemical Library Screening Shared Resource (CLS) (Core Group B) offers Cancer Center scientists the ability to develop and conduct small- and large-scale chemical library screens and perform hit optimization and validation for the generation of selective probes of biochemical and cellular processes of tumor biology. This resource, located within the large Conrad Prebys Center for Chemical Genomics at SBMRI (a national Comprehensive Center for both the NIH MLPCN and NCI CBC programs), provides Cancer Center faculty with access to technology, expertise and infrastructure resources to develop novel means for characterizing cellular targets involved in tumor pathogenesis and tumor onset and to advance the development of new lead molecules for anti-tumor therapies. CLS consists of four specialized but highly integrated facilities: 1) the High Throughput (HT) Assay Development Facility provides technical and scientific support in the development, miniaturization, and implementation of cell-based and biochemical HT assays, assists with characterization of compounds identified in primary screens through development and execution of secondary and orthogonal assays, as well as performs structure-activity-relationship, selectivity-panel and mechanism-of-action studies; 2) the Compound Management and HT Screening Facility manages the Institute's natural product and small molecule chemical compound libraries (over 700,000 compounds), maintains automation and detection equipment, and executes large-scale screening campaigns; 3) the High Content Screening Facility supports all aspects of development, execution, and image-data analysis of image-based high content screens, as well as aids with high-throughput microscopy assays for non-screening applications; and 4) the Medicinal Chemistry Facility provides technical support and expertise in the areas of medicinal chemistry, combinatorial chemistry, scale-up for advanced studies, and determination of physical properties. Over the past 5 years, a total of 36 Cancer Center members used the services of the CLS Shared Resource, carrying out 26 successful Cancer Center chemical biology projects, 12 advancing to hit-to-lead optimization, and 7 successfully generated leads with sufficient potency and drug-like properties to be explored in vivo animal models of disease. This direct access to experts and technology in chemical biology and early-stage drug development for CLS has provided consultation and technical sections for 57 grant proposals submitted by Sanford-Burnham Cancer Center PIs, of which 26 were awarded. CLS staff has been included in 44 Cancer Center member publications as co- authors, reflecting their important contribution to these scientific discoveries. In addition, data produced by CLS, access to chemical libraries and advanced instrumentation, consulting, and other services, contributed to at least 37 additional publications. The CCSG funding (10% of the total CLS budget), leverages substantial institutional investment in this extensive drug discovery infrastructure, and provides Cancer Center researchers with priority access to this technology strongly supporting both discovery and early translational research.